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Abstract: TH-PO504

AQP11 Plays a Role in Water Homeostasis in Concert with AQP4 in the Brain

Session Information

Category: Fluid and Electrolytes

  • 901 Fluid and Electrolytes: Basic

Authors

  • Ishibashi, Kenichi, Meiji Pharmceutical university, Kiyose, Japan
  • Sasaki, Sei, Tokyo Medical and Dental University, Bunkyo-ku, Japan
  • Tanaka, Yasuko, Meiji Pharmceutical university, Kiyose, Japan
Background

Water transport in the brain is tightly controlled by blood-brain-barrier (BBB) composed of endothelial cells (AQP1, 11) and glial foot processes (AQP4) where AQP4 regulates brain edema. Here we examined AQPs mRNA expression in acute hyponatremic or hypernatremic mice models of wild type and AQP11-null mice as AQP11-null mice suffer from renal failure which precludes chronic models.

Methods

By intraperitoneal injection, hypo- and hyper-natremic models were produced with water+desmopressin or 2M NaCl solution four or six hours before sacrifice, respectively. The expression of AQP1, 4 and 11 mRNA were quantified by RT-real-time PCR of whole brain RNA. Brain water content was calculated with 4-day-dried weight in 80 C oven and extravascular leakage by biotin permeability assay.

Results

In the control state, AQP11-null brain showed half AQP4 expression without AQP1 change as compared with wild mice (Na 153.3 vs. 150.7 mEq/L), whereas brain water content was similar (78.98 vs 78.61%). Acute hyponatremia (123.6 vs. 126.0 mEq/L) enhanced AQP4 expression in AQP11-null to the level of the wild mice with no change of AQP1, whereas it did not change AQP1, 4, nor 11 in wild mice. Brain water content was similar (79.93 vs. 79.8%) with expanded perivascular space, Virchow–Robin space. On the other hand, acute hypernatremia (199.5 vs. 208.0 mEq/L) increased AQP4 to the level of wild mice in AQP11-null with half AQP1 expression, whereas it decreased AQP1 and AQP11 by half without change in AQP4 in wild mice. Brain water content was significantly lower in AQP11-null than wild mice (75.34 vs. 76.65%) which was also documented histologically by cellular shrinkage in the brain cortex. Biotin permeability assay revealed no leakage in hypo- and hyper-natremic states. The results suggested that AQP4 expression was downregulated to match the decreased water transport at the endothelium in AQP11-null but may be enhanced to compensate for AQP11-null with osmotic changes although acute hypernatremia produced more water loss in AQP11-null brain.

Conclusion

We conclude that AQP11 may play a role in water homeostasis in concert with AQP4 at BBB with compensating enhanced AQP4 expression in AQP11-null with osmotic challenge. The results set a stage for examining the role of AQP11 in disease states such as brain edema. We are currently studying middle cerebral artery hemi-infarction model in AQP11 null mice.

Funding

  • Government Support - Non-U.S.